Sotorasib vs Durvalumab for Lung Cancer

Not currently recruiting at 11 trial locations

Overseen By Jamie Chaft, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Durvalumab

Disqualifiers: Pregnancy, Active malignancy, Prior pneumonitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for locally advanced non-small cell lung cancer. Researchers aim to determine if switching from the standard treatment, durvalumab (an immunotherapy drug), to sotorasib (a targeted therapy for KRAS mutations), can better control cancer in individuals with minimal residual disease (small amounts of cancer remaining after treatment). They will compare this switch to continuing with durvalumab. Suitable candidates for this trial have a specific type of lung cancer with a KRAS p.G12C mutation and have completed a course of chemoradiation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants will switch from durvalumab to sotorasib if they have detectable minimal residual disease. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sotorasib is generally safe for patients with advanced lung cancer. Studies indicate that adjusting the dose can manage any risks. In real-world use, patients with a specific genetic mutation (KRAS G12C) in their lung cancer usually tolerate sotorasib well. Another study found that sotorasib provided lasting benefits without introducing new safety issues for patients who had previous treatments.

Durvalumab, in contrast, is already approved for treating certain cancers, indicating it has undergone extensive safety testing. Overall, evidence shows that both treatments can be used safely, with known side effects that can be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sotorasib for lung cancer because it targets a specific mutation known as KRAS G12C, which is found in some lung cancer patients. Unlike traditional treatments, such as chemotherapy and immunotherapy like durvalumab, which broadly attack cancer cells or boost the immune system, sotorasib offers a more precise approach by directly inhibiting the mutated protein driving cancer growth. This targeted action not only holds the potential for better efficacy but also may lead to fewer side effects, as it spares healthy cells. This precision medicine approach represents a promising step forward in the treatment of lung cancer, offering hope for improved outcomes in patients with this specific mutation.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that sotorasib, one of the treatments studied in this trial for non-small cell lung cancer (NSCLC), has promising results. In earlier studies, patients with the KRAS G12C mutation had stable cancer for about 6.8 months on average and lived for about 12.5 months overall. Many patients experienced tumor shrinkage, with sotorasib shrinking or eliminating cancer in 41% of patients. These findings suggest that sotorasib could effectively manage lung cancer. Meanwhile, another group in this trial will continue standard care with durvalumab, which is also being evaluated for effectiveness in this context. ^{2 4 5 6 7}

Who Is on the Research Team?

Narek Shaverdian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with a type of lung cancer called locally advanced non-small cell lung cancer (LA-NSCLC). Participants should have minimal residual disease (MRD) detectable after initial treatment. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

My liver tests are within normal limits.

No evidence of radiographic progression as measured through SOC imaging

Therapeutic Phase:

Exclusion Criteria

Prior pneumonitis

Pregnant or lactating women

I haven't had any other cancer except for certain types in the last year.

Timeline for a Trial Participant

Pre-Monitoring

Patients with LANSCLC with a KRAS G12C mutation undergo chemoradiation and clinical assessments per standard of care.

Varies

Monitoring

Patients with detectable ctDNA post-chemoradiation start durvalumab consolidation and have ctDNA measured again early-on during durvalumab consolidation.

Approximately 6 weeks

Randomization

Patients are randomized to continue durvalumab or switch to sotorasib, with a 28-day washout period for those switching to sotorasib.

Up to 12 months for durvalumab, until progression for sotorasib

Follow-up

Participants are monitored for safety and effectiveness after treatment, with progression-free survival as a primary endpoint.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Sotorasib

Trial Overview The study tests if switching from durvalumab to sotorasib when MRD is detected can better control LA-NSCLC compared to staying on durvalumab alone. It's about finding the most effective treatment timing and combination for this condition.

How Is the Trial Designed?

Group I: switch sotorasib treatment until progression Experimental Treatment 1 Intervention

Will receive sotorasib at 960 mg daily until progression. A dose de-escalation regimen based on toxicity will be implemented as below. If 120 mg cannot be tolerated, sotorasib will be discontinued and the patient will be removed from the trial.

Group II: continue standard of care (SOC) durvalumab treatment Active Control 1 Intervention

Will continue to receive durvalumab, 10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a study of 26 patients with locally advanced non-small-cell lung cancer (NSCLC) receiving durvalumab after chemoradiation therapy, the median progression-free survival (PFS) was 15.6 months, indicating its efficacy in prolonging survival.

However, 73.6% of patients experienced pneumonitis, with a higher risk of grade 2 or above pneumonitis if durvalumab was started within 14 days after thoracic radiotherapy, suggesting careful timing and monitoring are crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer. Harada, D., Shimonishi, A., Saeki, K., et al.[2023]

In a study of 924 patients with unresectable stage III non-small cell lung cancer treated with durvalumab, race did not significantly affect treatment patterns such as initiation delays, interruptions, or discontinuations.

Black patients experienced fewer immune-related adverse events and pneumonitis compared to White patients, suggesting potential differences in safety profiles between racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. Moore, AM., Nooruddin, Z., Reveles, KR., et al.[2023]

Immune checkpoint inhibitors (ICIs), particularly durvalumab, have significantly improved treatment outcomes for patients with advanced non-small cell lung cancer (NSCLC), establishing them as the standard of care either alone or with chemotherapy.

Durvalumab is specifically approved as a consolidation treatment after chemo-radiotherapy for stage III NSCLC, highlighting its role in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. Gullapalli, S., Remon, J., Hendriks, LEL., et al.[2020]

Durvalumab, an anti-PD-L1 antibody, has shown effectiveness as both a standalone treatment and in combination with tremelimumab for advanced non-small cell lung cancer (NSCLC), demonstrating a well-tolerated safety profile in phase I and II studies.

The PACIFIC study confirmed that durvalumab significantly improves progression-free survival and overall survival when used as maintenance therapy after chemoradiotherapy for unresectable stage III NSCLC, leading to its FDA approval for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Murakami, S.[2020]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a study of 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000826

Real-world effectiveness and tolerability of sotorasib in ... Sotorasib has shown efficacy in a phase 3 trial compared to docetaxel among previously treated non-small cell lung cancer (NSCLC) patients with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39970524/

Real-world effectiveness and tolerability of sotorasib in ... This study gave insights into effectiveness and safety of sotorasib in a real-world setting, in advanced or metastatic KRAS G12C-mutated non-squamous NSCLC.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103695

Sotorasib for Lung Cancers with KRAS p.G12C Mutation The median progression-free survival was 6.8 months, and the median overall survival was 12.5 months. In addition, tumor shrinkage and disease control were ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02524

2-Year Analysis of CodeBreaK 100 Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 ...

5. nature.com nature.com/articles/s41591-025-03732-5

Molecular determinants of sotorasib clinical efficacy in ... Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39846981/

Pooled safety analysis and management of sotorasib-related ... Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03600883

NCT03600883 | A Phase 1/2, Study Evaluating the Safety, ... A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy